The structure of the ventral nerve cord of Caenorhabditis elegans.

The nervous system of Caenorhabditis elegans is arranged as a series of fibre bundles which run along internal hypodermal ridges. Most of the sensory integration takes place in a ring of nerve fibres which is wrapped round the pharynx in the head. The body muscles in the head are innervated by motor neurones in this nerve ring while those in the lower part of the body are innervated by a set of motor neurones in a longitudinal fibre bundle which joins the nerve ring, the ventral cord. These motor neurones can be put into five classes on the basis of their morphology and synaptic input. At any one point along the cord only one member from each class has neuromuscular junctions. Members of a given class are arranged in a regular linear sequence in the cord and have non-overlapping fields of motor synaptic activity, the transition between fields of adjacent neurones being sharp and well defined. Members of a given class form gap junctions with neighbouring members of the same class but never to motor neurones of another class. Three of the motor neurone classes receive their synaptic input from a set of interneurones coming from the nerve ring. These interneurones can in turn be grouped into four classes and each of three motor neurone classes receives its synaptic input from a unique combination of interneurone classes. The possible developmental and functional significance of these observations is discussed.     

Unequal competition between axons for neuronal targets.

Precise wiring of the nervous system depends not only on a matching between neurons and their synaptic targets, but also upon competition between neurons for particular targets. Neurons in adult leeches regenerate synaptic connections with their usual neuronal targets in the central nervous system, selecting only those targets with which they connect during embryogenesis. Thus during development axons of nociceptive (N) sensory cells make contacts on the cell bodies of certain neurons in adjacent ganglia but not upon those same types of cells in their own ganglion. After injury the N cell axons accurately regenerate contacts on the appropriate target cells. An abnormal feature observed after injury is that N cell axons sprout and grow to make contacts upon cell bodies within their own ganglion. This is a consequence of the normal innervation of those cells having been removed, thereby eliminating the source of competition. Similar competition during embryogenesis may guide the formation of selective connections.     

Ultrastructural characteristics of anterior gut innervation of Gallus gallus

The enteric nervous system of the bird's anterior gut is very well developed. Myelin fibres are seen accompanying the nervous trunks up to the mucous layer. Glial cells duplicate the number of neurons in the myenteric plexuses. Their number decreases at the submucous plexuses, but it is always higher than the neurons. Isolated neurons are widely spread in the circular muscle coat accompanying the nervous trunks which can be inter and intrafascicularly located. Direct synaptic contacts with the soma neuronal membranes are very often seen. We have never observed synaptic specializations. The most prominent varicosities either in the peripheric nervous trunk axons or directly laying on the soma membranes are those containing peptidergic or mixed vesicles of cholinergic and peptidergic types. The neurons show big nuclei of different size and shape. Neighbouring smooth muscle cells show abundant caveolae near the nervous elements. Although we have not observed close contacts with glands, thin axon bundles spread near the glandular cells of the mucous layer.     

Neurons and their interconnections in the frontal cortex of monkeys

It was shown by the Golgi and Golgi-Kopsch method that pyramidal cells of layers II–IV in the frontal cortex of the monkeyMacaca rhesus have numeruous, mainly recurrent axon collaterals by means of which they form vertical connections. Pyramidal cells with ascending axons are found. Axons of stellate basket neurons unite pyramidal cells in both horizontal (modules) and vertical (micromodules) directions; depending on the direction of the axon collaterals, two groups of stellate neurons can be distinguished. Groups of 14 to 16 pyramidal cells whose apical dendrites are connected into bundles were found. Axons of pyramidal cells in layers II–IV descend in the composition of the pyramidal tract and give off collaterals which run toward the bodies and dendrites of neighboring pyramidal cells, united into the same group, forming terminal and en passant junctions. Besides bundles, special kinds of "local" cell groups with U-shaped axons are found.A. A. Zhdanov Leningrad State University. Translated from Neirofiziologiya, Vol. 15, No. 2, pp. 115–120, March–April, 1983.     

In vivo imaging of presynaptic terminals and postsynaptic sites in the mouse submandibular ganglion

Much of what is currently known about the behavior of synapses in vivo has been learned at the mammalian neuromuscular junction, because it is large and accessible and also its postsynaptic acetylcholine receptors (AChRs) are readily labeled with a specific, high-affinity probe, alpha-bungarotoxin (BTX). Neuron-neuron synapses have thus far been much less accessible. We therefore developed techniques for imaging interneuronal synapses in an accessible ganglion in the peripheral nervous system. In the submandibular ganglion, individual preganglionic axons establish large numbers of axo-somatic synapses with postganglionic neurons. To visualize these sites of synaptic contact, presynaptic axons were imaged by using transgenic mice that express fluorescent protein in preganglionic neurons. The postsynaptic sites were visualized by labeling the acetylcholine receptor (AChR) alpha7 subunit with fluorescently tagged BTX. We developed in vivo methods to acquire three-dimensional image stacks of the axons and postsynaptic sites and then follow them over time. The submandibular ganglion is an ideal site to study the formation, elimination, and maintenance of synaptic connections between neurons in vivo.     

Molecular mechanisms of target specificity during synapse formation

Neurons are connected with a high degree of specificity in neuronal circuits. Axon guidance mechanisms are responsible for directing axons to their approximate target region. It is not well understood how precise synaptic connections form between specific pre- and postsynaptic neurons within the target area. Recent analysis of a group of cell surface proteins in different systems has shed light on the diverse cellular and molecular mechanisms that generate the precise patterns of connectivity.     

Structure of anterior dorsal ventricular ridge in snakes.

Anterior dorsal ventricular ridge (ADVR) is a major subcortical, telencephalic nucleus in snakes. Its structure was studied in Nissl, Golgi, and electron microscopic preparations in several species of snakes. Neurons in ADVR form a homogeneous population. They have large nuclei, scattered cisternae of rough endoplasmic reticulum in their cytoplasm, and bear dendrites from all portions of their somata. The dendrites have a moderate covering of pedunculated spines. Clusters of two to five cells with touching somata can be seen in Nissl, Golgi, and electron microscopic preparations. The area of apposition may contain a series of specialized junctions which resemble gap junctions. Three populations of axons can be identified in rapid Golgi preparations of snake ADVR. Type 1 axons course from the lateral forebrain bundle and bear small varicosities about 1 mu long. Type 2 axons arise from ADVR neurons and bear large varicosities about 5 mu long. The origin of the very thin type 3 axons is not known; they bear small varicosities about 1 mu long. The majority of axon terminals in ADVR are small (1 mu to 2 mu long), contain round synaptic vesicles, and form asymmetric active zones. This type of axon terminates on dendritic spines and shafts and on somata. A small percentage of terminals are large, 5 mu in length, contain round synaptic vesicles, and form asymmetric active zones. This type of axon terminates only on dendritic spines. A small percentage of terminals are small, contain pleomorphic synaptic vesicles, and form symmetric active zones. This type of axon terminates on dendritic shafts and on somata.     

Adult Rat Motor Neurons Do Not Re-Establish Electrical Coupling during Axonal Regeneration and Muscle Reinnervation

Gap junctions (GJs) between neurons are present in both the newborn and the adult nervous system, and although important roles have been suggested or demonstrated in a number of instances, in many other cases a full understanding of their physiological role is still missing. GJs are expressed in the rodent lumbar cord at birth and mediate both dye and electrical coupling between motor neurons. This expression has been proposed to mediate: (i) fast synchronization of motoneuronal spike activity, in turn linked to the process of refinement of neuromuscular connections, and (ii) slow synchronization of locomotor-like oscillatory activity. Soon after birth this coupling disappears. Since in the adult rat regeneration of motor fibers after peripheral nerve injury leads to a recapitulation of synaptic refinement at the target muscles, we tested whether GJs between motor neurons are transiently re-expressed. We found that in conditions of maximal responsiveness of lumbar motor neurons (such as no depression by anesthetics, decerebrate release of activity of subsets of motor neurons, use of temporal and spatial summation by antidromic and orthodromic stimulations, testing of large ensembles of motor neurons) no firing is observed in ventral root axons in response to antidromic spike invasion of nearby counterparts. We conclude that junctional coupling between motor neurons is not required for the refinement of neuromuscular innervation in the adult.     

The development of neuronal morphology in insects

Neurons are highly polarized cells with some regions specified for information input--typically the dendrites--and others specialized for information output--the axons. By extending to a specific location and branching in a specific manner, the processes of neurons determine at a fundamental level how the nervous system is wired to produce behavior. Recent studies suggest that relatively small changes in neuronal morphology could conceivably contribute to striking behavioral distinctions between invertebrate species. We review recent data that begin to shed light on how neurons extend dendrites to their targets and acquire their particular branching morphologies, drawing primarily on data from genetic model organisms. We speculate about how and why the actions of these genes might facilitate the diversification of dendritic morphology.     

Projections of Drosophila multidendritic neurons in the central nervous system: links with peripheral dendrite morphology

Neurons establish diverse dendritic morphologies during development, and a major challenge is to understand how these distinct developmental programs might relate to, and influence, neuronal function. Drosophila dendritic arborization (da) sensory neurons display class-specific dendritic morphology with extensive coverage of the body wall. To begin to build a basis for linking dendrite structure and function in this genetic system, we analyzed da neuron axon projections in embryonic and larval stages. We found that multiple parameters of axon morphology, including dorsoventral position, midline crossing and collateral branching, correlate with dendritic morphological class. We have identified a class-specific medial-lateral layering of axons in the central nervous system formed during embryonic development, which could allow different classes of da neurons to develop differential connectivity to second-order neurons. We have examined the effect of Robo family members on class-specific axon lamination, and have also taken a forward genetic approach to identify new genes involved in axon and dendrite development. For the latter, we screened the third chromosome at high resolution in vivo for mutations that affect class IV da neuron morphology. Several known loci, as well as putative novel mutations, were identified that contribute to sensory dendrite and/or axon patterning. This collection of mutants, together with anatomical data on dendrites and axons, should begin to permit studies of dendrite diversity in a combined developmental and functional context, and also provide a foundation for understanding shared and distinct mechanisms that control axon and dendrite morphology.     

Synaptic patterns in the dorsal lateral geniculate nucleus of the monkey

Summary Synaptic junctions are found in all parts of the nucleus, being almost as densely distributed between cell laminae as within these laminae.In addition to the six classical cell laminae, two thin intercalated laminae have been found which lie on each side of lamina 1. These laminae contain small neurons embedded in a zone of small neural processes and many axo-axonal synapses occur there.Three types of axon form synapses in all cell laminae and have been called RLP, RSD and F axons. RLP axons have large terminals which contain loosely packed round synaptic vesicles, RSD axons have small terminals which contain closely packed round vesicles and F axons have terminals intermediate in size containing many flattened vesicles.RLP axons are identified as retinogeniculate fibers. Their terminals are confined to the cell laminae, where they form filamentous contacts upon large dendrites and asymmetrical regular synaptic contacts (with a thin postsynaptic opacity) upon large dendrites and F axons. RSD axons terminate within the cellular laminae and also between them. They form asymmetrical regular synaptic contacts on small dendrites and on F axons. F axons, which also occur throughout the nucleus, form symmetrical regular contacts upon all portions of the geniculate neurons and with other F axons. At axo-axonal junctions the F axon is always postsynaptic.Supported by Grant R 01 NB 06662 from the USPHS and by funds of the Neurological Sciences Group of the Medical Research Council of Canada. Most of the observations were made while R. W. Guillery was a visiting professor in the Department of Physiology at the University of Montreal. We thank the Department of Physiology for their support and Mr. K. Watkins, Mrs. E. Langer and Mrs. B. Yelk for their skillful technical assistance.     

Nervous network in larvae of the ascidian Ciona intestinalis

 With the use of the monoclonal antibody UA301, which specifically recognizes the nervous system in ascidian larvae, the neuronal connections of the peripheral and central nervous systems in the ascidian Ciona intestinalis were observed. Three types of peripheral nervous system neurons were found: two located in the larval trunk and the other in the larval tail. These neurons were epidermal and their axons extended to the central nervous system and connected with the visceral ganglion directly or indirectly. The most rostral system (rostral trunk epidermal neurons, RTEN) was distributed bilateral-symmetrically. In addition, presumptive papillar neurons in palps were found which might be related to the RTEN. Another neuron group (apical trunk epidermal neurons, ATEN) was located in the apical part of the trunk. The caudal peripheral nervous system (caudal epidermal neurons, CEN) was located at the dorsal and ventral midline of the caudal epidermis. In the larval central nervous system, two major axon bundles were observed: one was of a photoreceptor complex and the other was connected with RTEN. These axon bundles joined in the posterior sensory vesicle, ran posteriorly through the visceral ganglion and branched into two caudal nerves which ran along the lateral walls of the caudal nerve tube. In addition, some immunopositive cells existed in the most proximal part of the caudal nerve tube and may be motoneurons. Received: 8 September 1997 / Accepted: 14 December 1997     

Ultrastructural features of the interrelationship between nerve fibers and the surrounding tissue in the major arteries of rabbits

The fine structure of nerve plexus in the rabbit abdominal aorta, ear and coronary arteries has been studied. Four types of the nerve fibre organization corresponding to different levels of sectioning their preterminal and terminal zones have been determined. Axons form large bundles which lose Schwann sheathes and divide into smaller and even single axons as they approach the distal end. Single axons make up contacts with effector cells without forming special synaptic structures. The smalles distance found between axon membranes and smooth muscle cells is 20 nm and 50 nm for the ear and coronary arteries, respectively. In the abdominal aorta, axons lie at a distance of several microns from the muscle sheath. Such arrangement supports the hypothesis of a "distant" nervous influence on the smooth muscle and indicates that the space of nervous influence comprises the tissue surrounding the blood vessel     

Differential appearance of dynamin in constitutive and regulated exo-endocytosis: a single-cell multiplex RT-PCR study

Neurons in the central nervous system establish, via their axons and dendrites, an extended network that allows synaptic transmission. During developmental maturation and process outgrowth, membrane turnover is necessary for the enlargement and subsequent growth of axons and dendrites from the perikarya to the target cell (constitutive exocytosis/endocytosis). After targeting and synapse formation, small synaptic vesicles are needed for the quantal release of neurotransmitters from the presynaptic terminal with subsequent recycling by regulated exocytosis/endocytosis. An investigation of the onset of the appearance of mRNA and protein in dissociated cultures of neurons from mouse hippocampus or from chick retina has shown an early abundance of proteins involved in exocytosis, such as syntaxin 1, SNAP-25, and synaptotagmin 1, whereas dynamin 1, a protein necessary for clathrin-mediated endocytosis, can be detected only after neurons have established contacts with neighboring cells. The results reveal that constitutive membrane incorporation and regulated synaptic transmitter release is mediated by the same neuronal proteins. Moreover, the data exclude that dynamin 1 takes part in constitutive recycling before synapse formation, but dynamin 2 is present at this stage. Thus, dynamin 2 may be the constitutive counterpart of dynamin 1 in growing neurons. Synapse establishment is linked to an upregulation of dynamin 1 and thereby represents the beginning of the regulated recycling of membranes back into the presynaptic terminal.     

Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons

Most neurons form synapses exclusively with other neurons, but little is known about the molecular mechanisms mediating synaptogenesis in the central nervous system. Using an in vitro system, we demonstrate that neuroligin-1 and -2, postsynaptically localized proteins, can trigger the de novo formation of presynaptic structure. Nonneuronal cells engineered to express neuroligins induce morphological and functional presynaptic differentiation in contacting axons. This activity can be inhibited by addition of a soluble version of beta-neurexin, a receptor for neuroligin. Furthermore, addition of soluble beta-neurexin to a coculture of defined pre- and postsynaptic CNS neurons inhibits synaptic vesicle clustering in axons contacting target neurons. Our results suggest that neuroligins are part of the machinery employed during the formation and remodeling of CNS synapses.     

Glial cells of the crayfish and their relationships with neurons. An ultrastructural study

1. Glial cells of the crayfish abdominal ganglia have been studied by transmission electron microscopy. Special attention is paid to the interrelationships between neurons and glial cells. Covers and hemocyte-related elements have also been considered. 2. Glial cells are identified by a common ultrastructure and close relationships with neurons. Four glial classes are considered, depending on their morphology, the compartment of neurons they ensheathe and neuron-glia interface. 3. Four ultrastructural classes of neurons are proposed. They differ in geometry and ultrastructure, as well as in glial covers (complexity and evaginations into the neuron somata). The morphology and organization of glial covers is specific for the neuron type they ensheathe. Specific glial covers do not differ in glia-glia communicatory structures. 4. The morphological and metabolical compartments of neurons are separated from the extracellular matrix or blood by specific glial systems. A system of two cells is interposed between neuron somata and hemolymph or the extracellular matrix. 5. Glial processes are crossed by membraneous tubular systems, at neuron perikarya and axons. Frequent gap junctions of varying area, density and number of IMP are found in the covers of neuron somata. 6. Neuron-glia interface bears numerous communicatory structures for both ionic and macromolecular exchange. They include junctions and transient modifications of membranes. Some of them suggest active transport mechanisms. 7. Modified endocytotic mechanisms seem to be responsible for the glia-to-neuron transfer of macromolecules as well as for the neuron-to-glia transfer of lamellar bodies. 8. The neuropil is divided into glomeruli (electrical or chemical) by glial processes and the trabeculae of the extracellular dense matrix. Neuron-glia membrane appositions have been found in electrical glomeruli. In chemical glomeruli, dense cored vesicles can release their content at neuron-neuron or neuron-glia intercellular cleft, at non-synaptic loci. 9. Neurons of type II contain peripheral complex Golgi systems, associated to subsurface cisternae and neuron-glia gap junctions, suggesting a cooperation of glial cells in specific macromolecular synthesis.     

Ultrastructural bases of the development of the neural apparatus of the heart

By means of electron microscopy developmental dynamics of the human and mammalian innervation has been studied during prenatal period of ontogenesis. Regularities in formation of the intracardiac nervous ganglia and in differentiation of nervous-muscular connections in the myocardium have been stated. Ultrastructural peculiarities of proneuroblasts and the nervous fiber terminals, growing to differentiating cardiomyocytes have been described during the premediator stage of the vegetative nervous system development. Peculiarities of synaptogenesis have been followed, among them those demonstrated as heterochromic formation of pre- and post-synaptic membrane and as uneven accumulation of synaptic vesicles. Development of the nervous-muscular connections have been studied. At the beginning of the mediator stage of the vegetative nervous system development formation of simple contacts between the nervous terminals and cardiomyocytes is intensified, and glial tunics develop rather poorly. Therefore, at the beginning the terminal parts of axons are not surrounded with processes of gliocytes. Simultaneously, formation of small intensively luminescent cells takes place. Development of afferent nervous terminals occurs not only in the myocardium, but in the intracardiac ganglia.     

Synaptic proteins and the assembly of synaptic junctions

Synapses are highly specialized contact sites between neurons and their target cells where information in the form of chemical substances travels from a pre- to a postsynaptic cell. In the central nervous system of mammals, most nerve cells are innervated by functionally distinct types of synapses, each requiring a specific set of molecular constituents for proper function. Various molecular players that may be involved in the assembly of synaptic junctions have been identified recently.     

Axon navigation in the mammalian primary olfactory pathway: where to next?

The process of establishing long-range neuronal connections can be divided into at least three discrete steps. First, axons need to be stimulated to grow and this growth must be towards appropriate targets. Second, after arriving at their target, axons need to be directed to their topographically appropriate position and in some cases, such as in cortical structures, they must grow radially to reach the correct laminar layer. Third, axons then arborize and form synaptic connections with only a defined subpopulation of potential post-synaptic partners. Attempts to understand these mechanisms in the visual system have been ongoing since pioneer studies in the 1940s highlighted the specificity of neuronal connections in the retino-tectal pathway. These classical systems-based approaches culminated in the 1990s with the discovery that Eph-ephrin repulsive interactions were involved in topographical mapping. In marked contrast, it was the cloning of the odorant receptor family that quickly led to a better understanding of axon targeting in the olfactory system. The last 10 years have seen the olfactory pathway rise in prominence as a model system for axon guidance. Once considered to be experimentally intractable, it is now providing a wealth of information on all aspects of axon guidance and targeting with implications not only for our understanding of these mechanisms in the olfactory system but also in other regions of the nervous system.